The objective of this research proposal is to develop an alternative and safe approach to immunotherapy of human T cell leukemia and lymphoma using the so-called internal image antigen, which is based on the idiotype network concept. According to the immune network hypothesis, certain anti-idiotype antibodies express three dimensional shapes which resemble the structures of external antigens and can induce specific immune responses similar to responses induced by external antigen. The starting point of our work to develop an idiotype vaccine was the availability of specific murine monoclonal antibodies against a relatively unique human T-cell leukemia/lymphoma-associated cell surface glycoprotein, GP-37 (MW 37,000) not found on normal T cells, or any normal organs, which represents an appropriate target for immunotherapy of T cell leukemia/lymphoma patients. This hybridoma has been used to generate monoclonal syngeneic anti-idiotype antibodies expressing the image of the tumor-associated antigen. To determine the vaccination potential of these anti-Id antibodies diFferent species of animals will be immunized with internal antigen or internal antigen coupled to a protein carrier for the production of anti-tumor immunity. Preclinical tests will include: the ability of the idiotype vaccine to induce in vitro cytotoxic T cells and antibody secretion by peripheral blood mononuclear cells from patients with T cell malignancies and appropriate control patients. Finally, we plan to study a limited number of patients with cutaneous T cell lymphoma in a phase I clinical trial to determine the effects of this type of therapy on various components of the immune system (both humoral and cellular) and try to identify the criteria to select patients who may benefit from anti-idiotype vaccine therapy. Patients will be monitored to determine the toxicity of the anti-idiotype vaccine and finally clinical responses Collectively, we hope these studies will lead to a novel idiotype approach to the therapy of human T cell leukemia/lymphoma and, at the same time, provide further insight into the biology of the immune network.